Prehabilitation in Older People Undergoing Total Hip Replacement

Introduction: Due to age, patients suffering from osteoarthritis (OA) experience a loss of skeletal muscle mass, strength, and functional capacity both before and after total hip arthroplasty (THA). Progressive resistance exercise training (RET) is a safe and feasible intervention before and after THA. However, the physiological and clinical effects have not been investigated on a larger scale.

Objectives: To determine the effect of RET-based (p)rehabilitation versus usual care on skeletal muscle mass and function, as well as on underlying biological processes, in older adults undergoing elective THA due to severe OA.

Materials and Methods: Seventy older adults scheduled for elective unilateral THA due to severe primary OA (usual care group: n=35, ≥60 years; (p)rehabilitation group: n=35, ≥60 years) will be included in this single-blind randomized controlled trial. Participants in the usual care group will undergo standard rehabilitation (12 weeks post-surgery), and participants in the (p)rehabilitation group will undergo RET-based full-body (p)rehabilitation (3x/week) for 2 weeks pre-surgery and 12 weeks post-surgery. MRI scans of the thigh will be taken at baseline, 24 hours before, and 12 weeks after surgery to assess the cross-sectional area of the quadriceps. On the same days, blood and muscle samples will be collected, and dual-energy X-ray absorptiometry (DEXA) will be performed. Maximum strength, muscle function/morphology, physical capacity, quality of life, performance in activities of daily living, physical activity level, hip function, nutritional status, and cognitive status will also be assessed. The occurrence of serious adverse events, hospital readmissions, infections, and complications will be considered.

In a sub-study, 20 participants (n=10 from the usual care group and n=10 from the (p)rehabilitation group) will be included to investigate the effects of 2 weeks of (p)rehabilitation on tissue protein synthesis rates. A 2-week deuterium oxide (²H₂O or "heavy water") loading protocol will be implemented in both groups during the two weeks prior to THA to assess musculoskeletal tissue protein synthesis rates. This method allows for the evaluation of the protein synthesis rate in muscle, cartilage, and bone tissue when samples are collected two weeks after the (p)rehabilitation or usual care interventions. These tissues will be collected during surgery, so no additional procedures are required from participants. In addition to determining the effects of RET on protein synthesis rates in tissues relevant to musculoskeletal health, the association between protein synthesis rates and long-term clinical outcomes will also be explored.

Expected Results: It is hypothesized that 14 weeks (2 weeks pre- and 12 weeks post-surgery) of progressive RET-based (p)rehabilitation will increase muscle mass and function to a greater extent than usual care, which is based on mobility and strength exercises without progressive machine-based RET. Additionally, RET will induce an increase in protein synthesis rates in muscle, cartilage, and bone tissues through the activation/inhibition of established signaling pathway markers (Akt, mTOR, S6(K), 4E-BP1, MAFbx, MuRF1). Furthermore, it is hypothesized that the increase in protein synthesis rate in these tissues will be associated with specific circulating biomarkers of musculoskeletal health (including CTX-II, COMP, CTX-I, OC, PIIINP, S1) and will indicate gains in muscle mass and functional improvements in the progressive RET group compared to the usual care group.

These findings will define the efficacy of progressive RET-based rehabilitation in increasing muscle mass and clinical outcomes in older adults with severe hip OA undergoing THA. Better maintenance or even increases in muscle mass and strength enhance independence, prolong health, aid recovery from illness, and reduce the burden on healthcare services. This information will have a beneficial impact on the fields of exercise physiology, orthopedics, and aging for future interventions at local, regional, national, and international levels.

• Change in functional capacity measured via Short Physical Performance Battery (SPPB) after resistance exercise training. [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.]
• Immunodetection of protein synthesis markers in tissue sample 2 weeks before surgery, during surgery and after resistance exercise training. [Time frame: The assessments will be conducted with the samples obtained 2 weeks before surgery, during surgery and after 12-week intervention.]
• Change in biomarkers measured via blood samples after resistance exercise training. [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.]
• Change in functional capacity measured via Timed Up and Go test (TUG) after resistance exercise training. [Time frame: The assessment will be conducted 2 weeks and 48 hours before and after the 12-week intervention]
• Change in muscle strength measured via 1RM strength tests after resistance exercise training. [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention]
• Change in body composition measured via dual-energy X-ray absorptiometry scanning after resistance exercise training [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention]
• Change in quality of life measured via SF-36 scale after resistance exercise training. [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.]
• Change in Independence in Activities of Daily Living via Lawton and Brody questionnaire after resistance exercise training. [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.]
• Change in Cognitive Function measured via MoCA questionnaire after resistance exercise training. [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.]
• Change in Nutritional Status measured via Mini Nutritional Assessment and Malnutrition Universal Screening Tool after resistance exercise training. [Time frame: The assessments will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.]
• Change in Perceived Hip Functionality measured via Harris Hip Score Questionnaire. [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after 12-week intervention.]
• Change in habitual physical activity measured via Physical Activity Scale for Elderly (PASE) after resistance exercise training [Time frame: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.]